Metastatic Breast Cancers on the Rise, U.S. Study Shows

 

• Incidence rates of de novo stage IV breast cancer increased overall from 2010 through 2021.
• The incidence of stage IV breast cancer increased significantly across sexes and age groups and numerically across all races and ethnicities.
• Overall survival among patients with stage IV disease improved in each successive year of the study.

Despite improvements in survival, the incidence of stage IV breast cancer increased significantly from 2010 through 2021, according to a U.S. population-based cohort study.

The age-adjusted incidence rate of de novo stage IV breast cancer significantly increased from 9.5 cases per 100,000 females in 2010 to 11.2 cases in 2021, an annual percentage change (APC) of 1.2% (95% CI 0.8-1.6), reported José P. Leone, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.

Among males, there was also a statistically significant increase in stage IV incidence, from 0.12 cases per 100,000 in 2010 to 0.20 cases in 2021, an APC of 3.7% (95% CI 1.0-6.5), they noted in JAMA Network Open.

Moreover, the incidence of stage IV breast cancer increased significantly across age groups and numerically across all races and ethnicities.

Notably, overall survival (OS) among patients with stage IV disease improved in each successive year, Leone and team reported.

"Prior analyses reported stable stage IV incidence before 2010 despite screening expansion," they wrote. "In contrast, our findings demonstrate a significant increase beginning in 2010, including among screening-eligible age groups. The underlying drivers remain uncertain and may reflect population-level changes in risk factors, screening patterns, or access to care."

"These findings suggest that efforts are needed to determine factors contributing to these increases and to identify breast cancer before patients present with de novo stage IV disease," they added.

In a commentary accompanying the study, Laura C. Pinheiro, PhD, MPH, of Weill Cornell Medicine in New York City, noted that while she agreed with the authors on the importance of identifying risk factors for the increasing incidence of stage IV disease, she also emphasized the need to "better support the multifaceted, complex needs of this growing patient population."

"Given the tremendous physical, psychosocial, and financial burden experienced by these patients, we should prioritize supporting adults with advanced cancer throughout the cancer care continuum," she wrote.

For this study, Leone and colleagues used data from the Surveillance, Epidemiology, and End Results (SEER) program to identify 761,471 patients diagnosed with de novo invasive breast cancer from January 2010 through December 2021. Median age at diagnosis was 60 years among all patients, and 63 years among those with stage IV disease; 99.2% were female, and 5.8% had stage IV disease.

The age-adjusted incidence of stages I to III disease also increased in females over the study time period, from 163.0 to 177.4 cases per 100,000 females, but the APC of 0.3% was not statistically significant (95% CI -0.3 to 0.9).

An analysis of stage IV incidence by tumor subtype showed statistically significant increases for triple-negative breast cancer (APC 2.7%, 95% CI 1.4-4.0), hormone receptor (HR)-positive/HER2-negative breast cancer (APC 2.0%, 95% CI 1.5-2.6), and HR-positive/HER2-positive disease (APC 1.6%, 95% CI 0.2-2.9). For HR-negative/HER2-positive disease, the APC was 1.3% (95% CI -0.1 to 2.7), a nonsignificant increase.

Patients younger than 40 years had the highest increase in overall incidence (APC 3.1%, 95% CI 2.2-4.0), which was driven by HR-positive cancers, while those older than 74 years had the highest increase in triple-negative cancers (APC 4.3%, 95% CI 1.9-6.8).

The age-adjusted incidence of stage IV breast cancer increased numerically across all racial and ethnic groups, and was highest overall among Asian and Pacific Islander patients (APC 3.4%, 95% CI 2.4-4.4).

OS improved significantly over time for each successive year among patients with HR-positive/HER2-negative disease (adjusted HR 0.99, 95% CI 0.98-0.99), HR-positive/HER2-positive disease (aHR 0.97, 95% CI 0.95-0.99), and HR-negative/HER2-positive disease (aHR 0.97, 95% CI 0.94-0.99).

The improvement in OS over time in triple-negative breast cancer was not statistically significant (aHR 0.99, 95% CI 0.97-1.01).

Leone and team said the improvement in OS across most subtypes likely reflected advances in systemic therapy, while the lack of a statistically significant improvement for triple-negative disease underscores "ongoing therapeutic challenges in this subgroup."

They acknowledged that their study had several limitations, including the fact that SEER does not have information on breast cancer screening use or adherence, or about epidemiological risk factors for breast cancer, such as obesity, breastfeeding, and hormone use.

"The absence of these variables limits our ability to assess how differences in screening practices, comorbidity burden, and individual-level socioeconomic or lifestyle factors may have contributed to observed incidence and stage-at-diagnosis trends," they wrote.

Disclosures

The study was supported by grants to Leone from the Catholic Health Foundation of Greater Boston, the Breast Cancer Research Foundation, a Conquer Cancer-Breast Cancer Research Foundation Advanced Clinical Research Award for Diversity and Inclusion in Breast Cancer, and the NIH.

Leone also reported receiving grants from Kazia Therapeutics, Lilly, Roche, and AstraZeneca, and receiving personal fees from Minerva Biotechnologies Consulting.

Several co-authors reported multiple relationships with industry.

Pinheiro reported receiving grants from the Pfizer/American Society of Clinical Oncology Conquer Cancer Foundation.

Primary Source

JAMA Network Open

Source Reference: Avila J, et al "Stage IV breast cancer incidence and survival, 2010-2021" JAMA Netw Open 2026; DOI: 10.1001/jamanetworkopen.2026.12042.

Secondary Source

JAMA Network Open

Source Reference: Pinheiro LC "Rising incidence of stage IV breast cancer -- are we prepared?" JAMA Netw Open 2026; DOI: 10.1001/jamanetworkopen.2026.12048.

https://www.medpagetoday.com/hematologyoncology/breastcancer/121235

Study on GLP-1s and Breast Cancer 'Too Good to Be True'?

 

• Patients with breast cancer and metabolic comorbidities have increased risks for cancer recurrence and death.
• This retrospective study suggested that GLP-1 agonist use for diabetes or obesity was associated with lower all-cause mortality and improved recurrence-free survival in breast cancer.
• However, outside experts raised a series of concerns about the study, including mortality effect sizes not seen in GLP-1 drug trials and missing data that could point to confounding from unmeasured factors.

Use of GLP-1 receptor agonists in breast cancer patients was linked to lower mortality and recurrence risk in a retrospective study, but experts are questioning the quality of the underlying data.

At 10 years, the risk of all-cause mortality in those with concurrent diabetes was 91% lower with GLP-1 agonist use compared with insulin or metformin use (HR 0.09, 95% CI 0.06-0.15). And for those with obesity, the risk was 65% lower compared with no GLP-1 drug use (HR 0.35, 95% CI 0.21-0.58), reported Bernard Fuemmeler, PhD, MPH, of the Massey Comprehensive Cancer Center in Richmond, Virginia, and colleagues.

Interestingly, no such association between GLP-1 agonist use and mortality was observed when compared with SGLT2 inhibitors in an unadjusted analysis (HR 0.97, 95% CI 0.82-1.14), according to the findings in JAMA Network Open, though adjustment for covariates showed a modest association with reduced mortality that favored GLP-1 use (HR 0.77, 95% CI 0.68-0.88).

The researchers, who noted that patients with breast cancer and metabolic comorbidities have increased risks of cancer recurrence and reduced survival, touted the results as "promising" and called for prospective studies "to understand the potential risks and the optimal timing and tailoring of GLP-1 RA [receptor agonist] treatment for patients with breast cancer."

However, in comments provided to the U.K. Science Media Centre, multiple experts raised questions about the study, pointing to outsized effects on mortality not seen in randomized trials of GLP-1 drugs and considerable gaps in the TriNetX database.

The results seem "too good to be true," said Paul Pharoah, MD, PhD, of Cedars-Sinai Medical Center in Los Angeles.

"There are some immediate red flags to suggest that the results are not a reliable indication of causality," he said. "The biggest red flag is that the effect sizes are enormous."

Beyond the roughly 90% relative reduction observed in mortality in the GLP-1 users with diabetes -- compared with insulin or metformin -- the study also reported reductions in the risk of breast cancer recurrence ranging from 56% to 67%, he noted.

"To put this in perspective, the most effective chemotherapy regimens reduce relapse by 38%," said Pharoah. "These effect sizes simply cannot be due to the drug and so the only reasonable explanation is confounding/bias."

Mangesh Thorat, MBBS, of Queen Mary University of London, noted areas of incomplete data, such as estrogen receptor (ER) status and treatment history in the patients' baseline characteristics.

"The ER status is known for around 20% of the population, whereas this figure should be near 100% in well-curated datasets," said Thorat. In addition, surgery information was available for fewer than 10% of the patients, while information on radiotherapy or systemic therapy use was available for fewer than 5% and around 25%, respectively.

For this study, Fuemmeler and colleagues used data from the TriNetX database for women with breast cancer from 68 U.S. healthcare organizations who received a diagnosis from April 2006 to April 2023, which followed the 2005 approval of GLP-1 drugs for diabetes management and included the 2021 approval for chronic weight management.

The study included 841,831 eligible patients with GLP-1 receptor agonist use (2 or more prescriptions) during the 6 months before and any time after their index breast cancer diagnosis. Mean age was 69.1 years, 71.7% were white, 12.1% were Black or African American, 5.6% were Hispanic or Latino, and 4.5% were Asian.

After exclusions and 1:1 propensity score matching, the three cohorts included 1,610 patients for GLP-1 drug use versus nonuse among patients with obesity (body mass index ≥30), and 2,323 patients for GLP-1 drug use versus insulin or metformin and 4,052 patients for GLP-1 drug use versus SGLT2 inhibitors among patients with type 2 diabetes.

The authors acknowledged that the study had limitations, including its retrospective design and reliance on a U.S. database, which limits generalizability.

Disclosures

The study was supported in part by the Virginia Commonwealth University Massey Comprehensive Cancer Center Biostatistics Shared Resource, which was supported in part with funding from a National Cancer Institute Cancer Center Support grant, and by the C. Kenneth and Dianne Wright Center for Clinical and Translational Research, supported in part by a Clinical and Translational Science Awards grant.

Fuemmeler had no disclosures.

Co-authors reported relationships with TriNetX, Hologic, Kubtec, and Axogen.

Primary Source

JAMA Network Open

Source Reference: Tatum KL, et al "Survival and recurrence with GLP-1 receptor agonists in breast cancer" JAMA Netw Open 2026; DOI: 10.1001/jamanetworkopen.2026.12133.

https://www.medpagetoday.com/hematologyoncology/breastcancer/121237

Last hantavirus outbreak devastated an entire village — how Argentina finally stopped it

 The MV Hondius cruise ship that became the epicenter of a hantavirus outbreak during its trans-Atlantic voyage set sail April 1 from Argentina, where painful memories of the deadly virus still linger from the last major outbreak nearly a decade ago.

Around 100 people attended a birthday party in the picturesque Patagonian village of Epuyén in November 2018, which became a superspreader event that ultimately killed 11 people.

It took severe quarantine measures to stop the spread.

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Mailen Valle, who lost her father and both of her sisters in a 2018-2019 hantavirus outbreak in Argentina.AFP via Getty Images

Centers for Disease Control and Prevention Acting Director Dr. Jay Bhattacharya said Sunday that US health officials were looking to protocols developed during past hantavirus outbreaks to contain the one from MV Hondius.

An infected guest — who was experiencing symptoms of the virus at the time of the party — transmitted the virus to several others seated nearby, leading to a cascading series of infections that sickened 34 others, according to a report in the New England Journal of Medicine.

“The person with the virus was just sitting at the same table as my dad. And at that table there were several people who got infected, and people died,” said Mailen Valle, 33, who lost her father and both of her sisters in the outbreak.

Tragically, Valle and her two sisters came down with hantavirus at their father’s funeral — one of them died “within hours” of showing symptoms, and the other was buried without a wake, she told France 24.

“Nobody was prepared to see how, in a matter of days, a family table was left empty,” she tearfully recalled to the outlet.

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The 2018-2019 outbreak originated at a birthday party in the Patagonian village of Epuyén.AFP via Getty Images

Isabel Diaz suffered the tragic loss of her mother — who was sickened by her father, Victor — in the outbreak.

He was later identified as “patient zero.”

“People looked poorly at my father. It’s not his fault he got sick,” she said to AFP, telling the outlet her family was discriminated against in the wake of the outbreak.

“Nobody chooses to get sick, much less infect others, much less lose a mother.”

Victor Diaz shared with the outlet that the virus caused body aches and left a taste in his mouth so bitter that even water was unpalatable to him.

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Bariloche Zonal Hospital in Argentina, where a patient infected with hantavirus is hospitalized.AFP via Getty Images

“It started with a feeling of weakness. I didn’t feel like eating. And I started to get purple spots,” he said. “That same day, I lost consciousness.”

Since the region’s outbreak of the virus — which locals have come to call simply “the hanta” — locals have taken measures to mitigate future potential outbreaks, including regularly airing out sheds and even scrubbing them with bleach.

Human-to-human transmission of the virus is generally rare; it’s most commonly spread through the urine, saliva or droppings of mice.

After the first 18 cases were confirmed, public health officials enforced strict isolation protocols on patients with confirmed cases, as well as self-quarantine of anyone with whom they might have come into contact.

The Journal of Medicine said “these measures most likely curtailed further spread,” which halved after isolation was ordered.

It became a preview of the quarantining the world would see less than two years later during the COVID-19 pandemic.

Unlike COVID, however, infectious disease experts say that human-to-human hantavirus transmission requires the exchange of large droplets of saliva — meaning only prolonged contact with an infected person is likely to lead to infection.

Bhattacharya said Sunday he believes that American passengers who were on the boat can be treated safely — and without an outbreak in the US — thanks to lessons learned in the previous outbreak.

“We want to treat it with our hantavirus protocols that were successful at containing outbreaks in the past,” he said.

In all, 34 people were confirmed infected in Argentina between November 2018 and February 2019, 11 of whom succumbed to the virus.

So far, three of the MV Hondius’ 147 passengers have died, and the rest are being closely monitored in their home countries after a multinational repatriation effort.

Of the 17 Americans who were aboard, 15 are being screened for symptoms at a quarantine facility in Nebraska, while the two patients known to be infected were flown to Emory University Hospital in Atlanta.

US health officials have repeatedly said the threat to public health from the isolated hantavirus outbreak is low, and will not lead to another COVID-19-like pandemic.

https://nypost.com/2026/05/12/world-news/how-argentina-stopped-the-last-hantavirus-outbreak/